Project Summary Cerebrovascular disease is a major source of stroke. However, clinicians treating patients with intracranial vascular disease are often in a quandary as to the most effective treatment as the underlying pathophysiology and likely progression is obscure. Until recently, non-invasive evaluation of the source of pathology - the vessel wall - was not possible. Although advances in Magnetic Resonance Imaging (MRI) technology show potential for vessel wall imaging (VWI), the true performance metrics of these approaches are poorly defined. The true resolution and the characterization of wall components, specifically inflammatory components, have not been established and vary among practitioners. This project will implement new approaches to in vivo intracranial VWI using high field strength MRI (at 3T and 7T). This goal will be achieved with theoretical design and simulations, in vitro models, in vivo implementation, with histology validation. First: we will optimize high-resolution (sub 0.5mm isotropic) 3D black blood fast-spin-echo MRI (termed SPACE on Siemens platforms) at 3T and 7T for whole brain intracranial VWI. The vessel wall signal to noise ratio, sharpness, and contrast to surrounding cerebrospinal fluid (CSF) or brain parenchyma will be simulated and optimized. This will be validated on in vitro models and with in vivo scanning of 10 healthy volunteers and 10 patients with intracranial vascular disease. We will also implement compressed sensing method to reduce the scan time of the long acquisition (currently around 10 minutes) to make it clinically feasible. Second: 3D SPACE, Ultra-short echo time (UTE) sequences and T2* mapping/quantitative susceptibility mapping (QSM) methods for detecting inflammation using Ultra-Small Super-Paramagnetic Iron Oxide (USPIO) contrast agents will be developed and validated in USPIO phantoms with a range of concentrations. These methods will be optimized to detect USPIO uptake in 10 patients with intracranial plaques, and the best approaches will be determined. Confirmation of the location of uptake assessed on imaging performed immediately prior to scheduled surgery will be sought on histology in 10 patients with intracranial aneurysms. Third: The ability of 3T imaging to characterize high-risk vessel wall features (such as intraplaque hemorrhage, intra-luminal thrombus, gadolinium enhancement, and USPIO uptake) will be assessed compared to scanning at 7T on 30 patients with cerebrovascular disease. Successful project conduct will provide methods to characterize the high-risk features of the intracranial vessel wall that could be clinically used to evaluate risk of stroke on a patient-specific basis and with a tool for validation across vendor platforms. These methods could be used to guide patient-specific therapy and improve stroke outcome ? directly supporting the mission of the National Heart, Lung, and Blood Institute.